Page 95 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

by tissue (0.5 dB/cm/MHz [88]) and the microbubble vibration is damped in blood [89]. In our in vitro study we incubated the HUVECs for 1 h with the SPIO. As the elimination half-life of EndoremTM (Feridex® in the USA) is 2.4 ± 0.2 h in humans and the SPIO are administered as a drip infusion over ~30 min [77, 90], it may be expected that the SPIO will circulate long enough in vivo to also achieve the 1 h incubation period. It was shown before that single cell tracking is possible by MRI using iron oxide as the label [13, 14, 16]. The micron-sized paramagnetic iron oxide (MPIO) particles used in one of these studies [13] are ten times bigger (1.6 μm) than SPIO. As it was revealed before [67] that the iron content of cells labeled with SPIO is less (~10 folds) than with MPIO, more cells may have to be labeled by SPIO to be detectable by MRI in vivo.
Conclusion
Our study shows that ultrasound-activated tMB are a promising technique to non-invasively enhance SPIO uptake by endothelial cells. From the current in vitro study, we derived optimal ultrasound parameters for SPIO delivery to HUVECs, that is, 40 kPa at 1 MHz (MI 0.04), 10,000 cycles and repetition rate of 20 Hz, applied for 30 s when SPIO were added at 0 min. This setting increased SPIO uptake up to 12 times compared to the control with 85% cell viability.
Acknowledgments
The authors are grateful to Prof. Dr. A.L. Klibanov from the University of Virginia, Cardiovascular Division, Charlottesville, Virginia, USA for discussions about the microbubble preparation. The authors thank Robert Beurskens, Kirby R. Lattwein, Michiel Manten, and Tom van Rooij from the Department of Biomedical Engineering, Erasmus MC, and Gabriela Doeswijk from the Department of Radiology & Nuclear Medicine, Erasmus MC, for technical assistance.
SPIO cell labeling using ultrasound
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